CN201643112U - Control system of multi-room-divided bioreactor - Google Patents
Control system of multi-room-divided bioreactor Download PDFInfo
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- CN201643112U CN201643112U CN201020148544XU CN201020148544U CN201643112U CN 201643112 U CN201643112 U CN 201643112U CN 201020148544X U CN201020148544X U CN 201020148544XU CN 201020148544 U CN201020148544 U CN 201020148544U CN 201643112 U CN201643112 U CN 201643112U
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Abstract
The utility model discloses a multi-room-divided bioreactor and a control system thereof. The utility model has the main improvement that reaction rooms formed in the bioreactor are divided into a plurality of relatively independent reaction regions, and an outlet passageway and an inlet passageway are improved, so that a second fluid can respectively flow into each reaction region in a gradient and degressive way, is independently reacted with a first fluid in each reaction region, and then flows out of the outlet passageway. Therefore, the multi-room-divided bioreactor comprehensively solves the problems of the uneven filling, the dead space, the blocking, the low exchanging efficiency and the like of the existing bioreactor.
Description
[technical field]
This utility model relates to field of biomedicine technology, relates in particular to a kind of multi-room separated bioreactor, control system.
[background technology]
Liver failure is the whole performance in latter stage of various hepatopathys, and conditions of patients is critical, case fatality rate height, prognosis extreme difference.Liver transplantation is the most effectively Therapeutic Method of generally acknowledging at present, but owing to reasons such as donor shortage, technical difficulty height, has greatly limited extensively carrying out of liver transplantation operation.Appearance based on the treatment meanss such as bioartificial liver of In vitro culture hepatocyte, be expected to once make the renal failure treatment produce revolutionary variation as artificial kidney, for the modern treatment of liver failure provides effective means, yet, appropriate design new-type bioreactor how, realizing external hepatocellular long-term large-scale culture, be still the bottleneck problem of present strong restrictions bioartificial liver's development, also is the important topic that needs to be resolved hurrily at present.
Bioreactor is bioartificial liver's core, and its performance is directly connected to the support effect of artificial liver.Research at present and numerous bioreactors of using mainly are divided into following several types, though existing part biological bioreactor of artificial liver has entered clinical experiment, do not have a kind of ideal bioreactor can fully satisfy the clinical application needs at present yet:
1, hollow fiber bioreactor: be a class reactor of studying at present and being most widely used.Its advantage is that foreign protein can be isolated, and prevents simultaneously in the human body at the lethal effect of the antigenic preexisting antibody of heterogenous cell to the loading cell.Thereby relatively more suitable heterogenous cell class (as porcine hepatocyte) bioreactor.Still there is following problem in this reactor at present: (1) volume is limited, and the cell useful load is little, and culture fluid and hepatocyte exchange area are limited, is unfavorable for external scale amplification; (2) side opening of semipermeable membrane is easily stopped up by cell mass, influences exchange efficiency, also is unfavorable for that the permanently effective of hepatocellular function and vigor keep; Therefore hollow fiber bioreactor is not best bioartificial liver's bioreactor.
2, flat plate bioreactors: such reactor is that hepatocyte is directly planted on flat board, its advantage is that cell distribution is even, the microenvironment unanimity, but surface to volume ratio descends, the reactor cell is a monolayer culture, can not permanently effective survival and keep function with active, and be difficult for amplifying, can't reach clinical requirement.
3, microcapsule suspension bioreactor: this bioreactor is that hepatocyte is wrapped up with a kind of semipermeable membrane material, make porous microcapsule, carry out perfusion cultures then. its advantage is that all cells has identical microenvironment, the space that a large amount of cell culture are arranged, reducing immunoreactive generation. shortcoming is because the existence of semipermeable membrane and the mutual gathering between hepatocyte cause the exchange of the inside and outside matter energy of capsule limited.In addition, Hoshiba[11] etc. research also show that hepatocyte is an anchorage-dependent cell, as lose attaching to timbering material, can inspire cell generation apoptosis.Therefore, this class bioreactor also is not that hepatocellular optimum selection is cultivated in external scale.
4, stirring type bioreactor is that a class is developed early and widely used perfusion bed/support bioreactor in research and production.This reactor is to make cell and timbering material reach suspended state by stirring, on the tank body top pick off is housed also, but parameters such as the temperature of continuous monitoring culture, pH, pO2, glucose consumption, its great advantage be can cultivate various types of zooblasts, culture process amplifies easily, but this bioreactor also has a fly in the ointment, be that mechanical agitation can produce certain shearing force, pair cell causes the damage of going up largely easily, thereby has limited its further utilization.
In view of analysis, be necessary to use for reference some prior aries and be optimized present all kinds bioreactor mentality of designing.
See also disclosed US5989913 patent application on November 23rd, 1999, its disclosed a kind of incubator, this incubator comprises: tubular vessel, have first and second end walls and place a cylindrical wall between these two end walls, one inlet, an outlet, and first and second filters, described first and second filters have a plurality of openings, this opening allow fluid medium and cellular metabolism waste material by and stop cell and cell cluster to pass through; One culturing room, by described cylindrical wall, first and second end walls, and described first and second filters define jointly, and this culturing room has a penetrating fore and aft axis; One device is used for rotating this tubular vessel around the fore and aft axis of level; One pump is used to keep liquid culture medium arteries and veins stream by this culturing room.
Design and be applied to the rotating and culturing system (RCCS) of microgravity life science at present by NASA (NASA), through nearly twenties years correlational study, success applies in a plurality of field of tissue engineering technology such as rabbit corneal cell, Skeletal Muscle Cell, osteoblast widely.Up-to-date member's rotary pouring microgravity bioreactor (RCMW) in its series of products, have and aforementioned US5989913 patent application corresponding structure, can horizontally rotate by culture vessel and reach the microcarrier that makes in the container and cell and overcome gravity and reach suspended state, and realize the two-way circulation of oxygen in the container, nutrient substance and metabolite by external peristaltic pump.But the applicant finds that in the process of in earlier stage using this bioreactor still there are bottleneck problems such as nutrition supply deficiency, perfusion heterogeneity and easy obstruction at present in this reactor, mainly shows:
At first, it is low to cultivate the interior two-way mass exchange efficient of vessel: all coated by filter membrane owing to cultivate the outlet and the inlet of the fore and aft axis of vessel inside, cause a part of culture medium pass behind the filter membrane with the outer culturing room of film in culture medium carry out the exchange of nutrient and oxygen, realize " effectively circulation "; Another part culture medium is a passage with the gap between filter membrane and this fore and aft axis then, directly flows out and cultivates outside the vessel, can not finish the function of nutrient and oxygen exchange, can cause cultivating the cell tissue nutrition supply deficiency in the vessel, becomes " invalid circulation ".
Secondly, perfusion heterogeneity in the culture vessel, there is dead space: in the RCMW circulation pattern, the permeability that increases filter membrane helps to improve the filter membrane outer circulation, reduces " invalid circulation ", but because the fluid pressure of culture vessel central authorities (pivot center place) is lower than the fluid pressure of its periphery, make the culture medium flow velocity of culture vessel central authorities and change speed very fast, container periphery culture medium flow velocity and replacing speed are slower, cause the perfusion heterogeneity in the container, form dead space in the culture vessel periphery.
Moreover in the RCMW circulation pattern, because liquid circulation flows to singlely in the culture vessel, (outlet is 4 small side holes) concentrated in the little and position of culture fluid discharge area, thereby causes cell and microcarrier in the exit position blocking problem.
[utility model content]
The purpose of this utility model is to provide a kind of exchange efficiency and uniformity coefficient can strengthen two kinds of fluids that participate in reaction and exchange the time, and insufficient multi-room separated bioreactor, control systems such as dead space that exists when overcoming exchange and obstruction;
For realizing this purpose, this utility model adopts following technical scheme:
A kind of multi-room separated bioreactor, control system comprises:
Bioreactor, it comprises cylindrical shell, mandrel and filter membrane, cylindrical shell forms reative cell and reacts to offer first fluid that has fused first material and second fluid that has fused second material, mandrel traverses drum shaft to setting, the mandrel two ends form second fluidic entry and the exit passageway respectively, this filter membrane coats this mandrel, to stop first material, to allow second material to pass through, forms the slit between filter membrane and the mandrel;
Motor is used to drive described bioreactor around its mandrel rotation;
Storage bottle is used to store second fluid that has fused second material;
Kinetic pump, second fluid that is used for keeping storage bottle enters reative cell after exit passageway is got back to storage bottle to constitute unidirectional closed circuit through the entry of bioreactor;
In this bioreactor, along be coated with filter membrane mandrel be axially arranged with at least two ligation parts reative cell is divided into a plurality of reaction zones, this ligation part is provided with axis hole and passes through for the mandrel that is coated with filter membrane, the radius of ligation part accounts for 3/10 to 7/10 barrier part radius;
Described exit passageway and access road all are connected with each reaction zone separately.
This mandrel comprises urceolus and inner core, urceolus hollow, and its two ends and cylindrical shell end walls fix, the sealing of one end, the other end is formed with the outer side outlet of described exit passageway, and its surface is axially arranged with some through holes to form the interior side outlet of described exit passageway along it;
Described inner core hollow, its end opposite sealing with the urceolus blind end, the other end and corresponding cylindrical shell end wall fix and form the outer side entrance of described access road, and its surface is axially arranged with some through holes to form the interior side entrance of described access road along it;
The pairing mandrel of each described reaction zone place is equipped with described interior side entrance and interior side outlet.
Preferable, the radius of described ligation part accounts for 1/2 barrier part radius.
Described cylindrical shell is provided with sample tap and application of sample mouth.
This control system also comprises oxygenator, and being used for provides oxygen that the source provides and second fluid of described closed circuit to be combined to oxygen.This oxygenator comprises a cylindrical shell, cylindrical shell has a wall and two headwalls reach by they defined synthetic chambeies, synthetic intracavity is provided with the group of fibers of being made up of side by side many doughnuts, the both sides of the longitudinally of this group of fibers and synthetic chamber cementation are to form the liquid stream chamber of passing through for second fluid between cementation position, two places, the hollow cavity of each doughnut forms the airflow chamber that oxygen supply gas passes through jointly, cylindrical shell is provided with air inlet and the gas outlet that is communicated with this airflow chamber, and is provided with inlet and the liquid outlet that is communicated with this liquid stream chamber.The cross section at described inlet and liquid outlet place is provided with buffer board and enters the liquid stream chamber so that second fluid presents with the non-rectilinear path.
Compared with prior art, this utility model possesses following advantage:
At first, this utility model carries out the many places ligation by a plurality of ligation parts that use has larger sectional area to the reactor inner spindle, reative cell in the reactor is divided into a plurality of reaction zones (room), connected relation in conjunction with exit passageway and each reaction zone, make each reaction zone all can independently finish the first fluid and the second fluidic exchange, and be connected by periphery between each reaction zone, overcome " invalid circulation " phenomenon on the one hand, on the other hand, the refinement reative cell is a plurality of reaction zones, and exchange between the first fluid and second fluid or reaction can be more careful, fully.
Secondly, the urceolus of mandrel is provided with a plurality of through holes vertically, relatively large first material of diameter and first fluid thereof only can only not accumulate in several through holes in the reative cell, so just can not cause of the obstruction of first material, guarantee the operate as normal of bioreactor, control system at the exit passageway place.
In addition, improved the oxygenator of structure, make flow through wherein oxygen can be fully and second fluid in the closed circuit fuse, and can control effectively to the oxygen-supplying amount that enters this kind oxygenator in conjunction with corresponding control approach, undoubtedly, the quantitative management of realizing bioreactor, control system there be bigger benefiting.
[description of drawings]
Fig. 1 is the sectional side elevation of bioreactor of the present utility model, and its internal structure is shown;
Fig. 2 is the middle B part enlarged drawing of Fig. 1;
Fig. 3 is the structural representation of multi-room separated bioreactor, control system of the present utility model;
Fig. 4 is the sectional side elevation of the oxygenator of an embodiment of the present utility model, and its internal structure is shown.
[specific embodiment]
Below in conjunction with drawings and Examples this utility model is further described:
Biochemical reaction can take place between the first fluid that this utility model is alleged and second fluid, carry out in two kinds of fluids of biochemical reaction at needs, after biochemical reaction takes place with two of fluid in one of fluid, one of them can become object, and this object is the object of the purpose that reaches certain preparation or treatment.The biochemical reaction that is carried out, saying is because second (class) material that first (class) material that first fluid fused or existed and second fluid fuse or exist reacts each other more specifically.For example, the cell culture stage when the simulation bioartificial liver, earlier in bioreactor perfusion fused treat cultured cell culture medium as first fluid, first material wherein is cell, make the culture medium that has fused nutrient (aminoacid, glucose etc.) and oxygen pass through this bioreactor again as second fluid, so that the cell for the treatment of in the bioreactor is cultivated, nutrient wherein and oxygen are second (class) material.Routine again, treatment stage when the simulation bioartificial liver, dabbling first fluid is the health blood that comprises healthy cell in bioreactor, healthy cell becomes first (class) material herein, second fluid by this bioreactor then is a blood samples of patients, metabolic waste in the blood samples of patients and toxin become second (class) material at this moment, when fusing with first fluid, metabolic waste and toxin are all engulfed by the healthy blood cell, and effusive second fluid will become healthy relatively blood from bioreactor.More than two examples, disclose two kinds of biochemical reactions that bioreactor of the present utility model inside is carried out jointly, all be to utilize celelular mechanism to implement.In like manner, those skilled in the art should know, and bioreactor of the present utility model also can be applied to the occasion of other biochemical reaction.
By above two examples as can be seen, the first fluid of the present utility model and second fluid generally are of identical composition, for example aforesaid culture medium, and second fluid can change to some extent through the composition before and after the bioreactor, show that mainly second material (nutrient and/or oxygen) can biochemical reaction take place with first material (cell) in the reative cell and causes second amount of substance to become or disappear, and exchange also may take place in total part wherein such as culture medium between the first fluid and second fluid.When second fluid initially provides, its second material only comprises some nutrients, and when dissolved in oxygen in this second fluid after, then its second material just comprises nutrient and oxygen simultaneously, when second fluid when biological reactor stream goes out, part second material wherein falls sharply even disappears.As seen, as kinematic concepts, the variation of composition should not influence the understanding to this utility model difference " fluid ".
To serve as main being described with aforementioned first example below this utility model, also be, taked to fuse treat cultured cell culture medium as first fluid, the culture medium of having taked to comprise nutrient and oxygen is as second fluid, thus, reative cell in the following bioreactor also can be referred to as culturing room, so that its name more meets those skilled in the art's custom.
Please consult Fig. 3 earlier, this figure has disclosed the structure of bioreactor, control system of the present utility model, and this control system comprises bioreactor 50, motor 56, kinetic pump 54, oxygenator 53 and storage bottle 51, the common formation of these parts one closed circuit.Below disclose in detail each ingredient of bioreactor, control system.
Please in conjunction with Fig. 1 and Fig. 2, Fig. 2 is a B part enlarged drawing among Fig. 1.Described bioreactor 50, its integral body is tubular, comprises cylindrical shell 1, mandrel 3 and filter membrane 2.
The end walls 11,12 that mandrel 3 traverses cylindrical shell 1 is provided with, and the axis of mandrel 3 preferably and the dead in line of cylindrical shell 1.Mandrel 3 has the inner/outer tube structure, its urceolus 301 is hollow tubular, axially on barrel, be formed with a plurality of through holes with side outlet in forming 323 along it, and an end is communicated to outside second end wall 12 to form outer side outlet 320, the sealing when other end then is connected with post jamb 12.Thus, whole urceolus 301 from interior side outlet 323 to urceolus 301 hollow bulbs 3010 again to exit passageway 32 of outer side outlet 320 formation.The inner core 302 of an external diameter much smaller than the internal diameter of urceolus 301 also installed in mandrel 3 inside, and inner core 302 also has hollow bulb 3020, and its end near second end wall 12 is sealed, and an end of close first end wall 11 is opening then.In like manner, this inner core 302 along its axially barrel be provided with a plurality of through holes with form a plurality of in side entrances 313, its open side is connected with first end wall 11 to form side entrance 310 outside in first end wall, 11 outsides, and side entrance 310 to the hollow bulb 3020 of inner core 302 just forms an entry 31 to interior side entrance 313 again outside it.Thus, mandrel 3 two ends form respectively for the culture medium (second fluid) that has fused nutrient and oxygen and enter the entry 31 of this reative cell 10 and supply to participate in reacted culture medium (second fluid) autoreaction chamber 10 effusive exit passageways 32.The length that a preferable scheme is an inner core 302 should be set at least more than or equal to 1/2 urceolus, 301 length, like this, entry 31 just has long span, and second fluid in entry 31 is able to inject reative cell 10 from the shunting of successively decreasing of the lateral attitude gradient type of the relative broad of reative cell 10; Urceolus 301 is owing to occupy the axial of entire reaction chamber 10, and its second fluid also can enter exit passageway 32 relatively equably from its whole barrel.As seen, no matter exit passageway 32 still is an entry 31, because its be second fluid design in reative cell 10 a plurality of outlets or inlet makes that first materials in the reative cell 10 can not gather in certain, has eliminated the possibility of stopping up to large extent.
As can be seen, because urceolus 301 hollows, and second fluid of the outer side entrance 310 by inner core 302 needs refer to especially that through the exit passageway 32 of urceolus 301 hollow bulb 3010 of urceolus 301 enters reative cell 10, on the other hand, participating in reacted second fluid needs to enter exit passageway 32 via the interior side outlet 323 of urceolus 301, so, the through hole on urceolus 301 surfaces has the two-way effect of passing through simultaneously in fact, promptly both allow unreacted second fluid to enter reative cell 10, and allowed reacted second fluid to enter exit passageway 32 again.
This filter membrane 2 is tubular because of the cylinder of the urceolus 301 that is coated on this mandrel 3, filter membrane 2 surfaces are formed with the moderate a plurality of miniature aperture in aperture, so that stop aforementioned first fluid especially first material pass through, and allow aforesaid second fluid especially second material pass through, particularly, because the diameter of cell is big than nutrient and oxygen molecule,, can realize this function so the aperture size of filter membrane 2 is arranged on less than first material size in the size range greater than the second material size.Filter membrane 2 is because its structure is lax relatively, the character softness, so with easy formation slit 20 between the mandrel 3.So, after second fluid entered from entry 31, a part can see through filter membrane 2 and enter reative cell 10.As shown in Figure 1, on filter membrane 2 longitudinallies, adopt a plurality of ligation parts 400 equidistantly to arrange filter membrane 2 formed tubulars are carried out ligation, thus, filter membrane 2 is at a plurality of ligation position and mandrel 3 banding and fitting tightly mutually, and described slit 20 just is divided into disconnected a plurality of crack district 208 mutually, because of 208 in a plurality of crack district is not communicated with each other, after so second fluid enters reative cell 10, will all enter and participate in the reative cell 10 flowing out again after the reaction, so can make the exchange rate enhancing of itself and first fluid.
The cross section of this ligation part 400 is positive circle, and the center is provided with axis hole (not label) and passes through for the mandrel 3 of band filter membrane 2, and the size of this axis hole just makes ligation part 400 compressing filter membranes 2 and mandrel 3 banding mutually.This ligation part 400 is designed to round pie, it radially has certain width, it is the radius that the radius of ligation part 400 preferably was slightly larger than or was slightly less than reactor shell 1, in theory, if cylindrical shell 1 radius is R, then ligation part radius r can be between 0.3R to 0.7R value, certainly, best numerical value is r=R/2.Ligation part 400 in the present embodiment needs to adopt the hard material with certain rigidity, the material of unlikely distortion all can as long as can satisfy the certain fluid scouring power of opposing as various hard metals, plank, plastics, pottery etc., preferable, tend to adopt metal material.The setting of a plurality of ligation parts 400 that surface area is bigger, reative cell 10 is divided into a plurality of reaction zones 108 that are short cylindrical, the periphery of each reaction zone 108 interconnects again, and it is independent to side outlet 323 in interior side entrance 313 of part and the part should be arranged, has relative independentability between each reaction zone 108, just as a plurality of small-sized reative cells.Because reaction zone 108 miniaturizations and relatively independent, make second fluid that enters from exit passageway 32 to carry out biochemical reaction with the first fluid that the gradient level is diverted to a plurality of reaction zones 108 with each reaction zone 108, then, second fluid of finishing reaction in each reaction zone 108 can directly enter exit passageway 32 by side outlet 323 in corresponding again and flow out, large-scale reative cell 10 is by refinement, can make that therefore the biochemical reaction that is carried out in the entire reaction chamber 10 is more even abundant.
Please consult Fig. 1 again, in order to strengthen the relation of being close to of filter membrane 2 and mandrel 3 urceolus 301, can further adopt less 402 pairs of close two end walls 11 of ligation part in cross section of elastic tape and so on, ligation is carried out in 12 position, certainly, the shape of ligation part herein can flexible design be that the larger area shape is shown in 401.
In addition,, one sample tap 14 and an application of sample mouth 15 are set respectively, with the tight respectively lid of plug part 140,150, only just open plug part 140,150 when needed and used at ordinary times in any position, cylindrical shell 1 post jamb, 13 place for the ease of sampling and application of sample from reative cell 10.
Please in conjunction with Fig. 3, motor 56 of the present utility model is mainly used in the described bioreactor 50 of driving and is rotated around its axis, because the axis of mandrel 3 overlaps substantially with the axis of the barrier part 1 of bioreactor 50, axis rotation mandrel 3 around mandrel 3 promptly turns whole barrier part 1 in fact, thereby realizes the rotation of whole bioreactor 50.Rotation direction can be unidirectional also can be two-way, the rotation direction of motor 56 does not influence enforcement of the present utility model.
In this utility model multi-room separated bioreactor, control system, storage bottle 51 is communicated with respectively to form unidirectional closed circuit with the outer side entrance 310 and the outer side outlet 320 of bioreactor 50 by pipeline, so need in this closed circuit, to utilize a kinetic pump 54 to drive the circulation of second fluid in this loop of storage bottle 51, in order to make in the storage bottle 51 culture medium carry sufficient amount of oxygen, also needing provide the oxygen composition in the source (not shown) to fuse in second fluid in this loop natural air or oxygen in conjunction with at least one oxygenator 53.
Multi-room separated bioreactor, control system of the present utility model uses and realizes with following structure and mode: its at first in storage bottle 51 splendid attire fused the culture medium solution of nutrient as second fluid, in bioreactor 50 splendid attire comprised treat cultured cell culture medium solution as first fluid, with structure as shown in Figure 5, by two pipelines that draw from storage bottle 51, one of pipeline is communicated with to carry out oxygen herein synthetic earlier with oxygenator 53, be connected with kinetic pump 54 by oxygenator 53 again and promote that to apply herein second fluid carries out circulation power, then, be connected by the outer side entrance 311 of kinetic pump 54 with the entry 31 of bioreactor 50, outer side outlet 321 with the exit passageway 32 of bioreactor 50 directly is connected with storage bottle 51 by another pipeline again, can finish the physical connection of The whole control system.
During work, under the driving of kinetic pump 54, the culture medium of having carried nutrient is from storage bottle 51, arriving one of by the road oxygenator 53 mixes with oxygen, subsequently in the outer side entrance 310 of the entry 31 from the culture medium that has fused nutrient and oxygen that oxygenator 53 comes out enters bioreactor 50 Fig. 3 through kinetic pump 54 on the left of, second fluid enters reative cell 10 then and carries out biochemical reaction with first fluid, after cell in the first fluid has absorbed nutrient and oxygen in second fluid, the outer side outlet 320 of the exit passageway 32 on second fluid right side in Fig. 3 is back in the storage bottle 51, finishes a circulation.Wherein, oxygenator 52,53 is the work that participates in real time with kinetic pump 54.
It should be noted that, in the control system of the present utility model, exit passageway 32 positions and entry 31 positions of bioreactor 50 are fixed, as shown in Figure 1, the entry 31 of bioreactor 50 is provided with on the right side, exit passageway 32 is provided with in the left side, this position relation is constant, so kinetic pump 54 need be connected with the outer side entrance 310 of the entry 31 on right side shown in Figure 2 (although the definition left side is entry in Fig. 3), the outer side outlet 320 of the exit passageway 32 of bioreactor 50 (Fig. 1 left side) then directly is connected with storage bottle 51.If exchange the position of exit passageway 32 and entry 31, also be exchange current to, then may cause the left side enters from Fig. 1 second fluid can't overcome resistance right side from Fig. 1 and flow out, obvious this mode is runed counter to original intention of the present utility model.
Described two headwalls 61,62 and the tube wall 60 between, defined a synthetic chamber 63 in cylindrical shell 6 inside, should be provided with the group of fibers 620 of trooping side by side and making in the synthetic chamber 63 by many doughnuts, every doughnut in the group of fibers 620 all is parallel to the axis setting of cylindrical shell 6 with its longitudinally, so can be understood as the longitudinally of group of fibers 620 and axially paralleling of cylindrical shell 6.There is the gap between doughnut and the doughnut.The chamber wall in the synthetic chamber 63 of the both sides of the axis direction of group of fibers 620 and this cylindrical shell 6 seals with the viscose glue cementation, locate 64 places, cementation position 620 liang of group of fibers, between each doughnut also by cementation in the hope of the integral sealing of group of fibers 620 outsides at this place, the gap has been by just having constituted a liquid stream chamber 632 that belongs to these synthetic chamber 63 parts between fiber between the cementation position, two places 64 and fiber, and the hollow cavity of each doughnut just constitutes the airflow chamber 631 that belongs to these synthetic chamber 63 another part jointly.As everyone knows, doughnut in a tubular form, the relative gas of fiber tube wall has penetrance, liquid then has sealing relatively, when so gas can pass through at the hollow cavity of each fiber, part gas can penetrate the fiber tube wall, and liquid then can not penetrate the fiber tube wall and enter its hollow cavity.
But the airflow chamber 631 and the liquid stream chamber 632 that are made of jointly group of fibers 620 and cylindrical shell 6 have the architectural feature that non-overlapping copies staggers mutually.In the cross section visual angle of cylindrical shell 6, liquid stream chamber 632 surrounds airflow chamber 631 basically and is provided with, or being provided with for surrounding a plurality of more tiny airflow chamber of looking.
As previously mentioned, airflow chamber 631 is used for by oxygen, and liquid stream chamber 632 is used for by culture fluid (second fluid).Make fluid liquid stream chamber 632 in, to circulate because of half permeation of group of fibers 620 between airflow chamber 631 and the liquid stream chamber 632 and can not pass the doughnut tube wall and enter airflow chamber 631, and the oxygen of airflow chamber 631 can penetrate the doughnut tube wall and enters liquid stream chamber 632 and fuse mutually with culture fluid.Therefore, in liquid stream chamber 632, gas and fluid have carried out biochemical reaction, and because of cylindrical shell 6 air-tightness own are good, gas can not leak into cylindrical shell 6 outsides.
For oxygen being provided for airflow chamber 631, a described headwall 61 is provided with air inlet 616, another headwall 12 is provided with gas outlet 626, air inlet 616 all is connected with this airflow chamber 631 with gas outlet 626, but between the respective end of headwall 61 and group of fibers 620, and between the respective end of headwall 62 and group of fibers 620, also be formed with one the buffering crack, after this buffering crack supplied gas enters wherein again every trade advance.Because of air inlet 616 and gas outlet 626 are distance with the lengthwise span of cylindrical shell 6, so have the abundant exercise range to flow out this airflow chamber 631 after oxygen enters airflow chamber 631, again because of having the gap between each doughnut, be equivalent to the contact area that has increased airflow chamber 631 and liquid stream chamber 632, oxygen has time enough and contact area to pass group of fibers 620 to fuse mutually with fluid in the liquid stream chamber 632 is more abundant during this period.
For culture fluid being provided for liquid stream chamber 632, in conjunction with liquid stream chamber 632 basic construction featuress of surrounding airflow chamber 631, at a distance of the position inlet 606 and a liquid outlet 608 are set respectively at any two places of the outer wall of tube wall 60, inlet 606 and liquid outlet 608 all are connected with liquid stream chamber 632, after the fluid that enters by inlet 606 just can enter liquid stream chamber 632 and mixes with oxygen, flow out through liquid outlet 608 again.
The design of inlet 606 and liquid outlet 608 makes it present a straight line path separately; enter and from liquid outlet 608 effusive fluids from inlet 606; generally be to drive by kinetic pump (not shown); therefore; unmanageable flow velocity can bring certain influence to nutrient in the culture medium and soft group of fibers 620; particularly when flow velocity is higher; relative group of fibers 620; it is bigger to enter fluidic momentum along linear passages; can cause group of fibers 620 distortion or destruction; for fear of this kind situation; in inlet 606 and liquid outlet 608; the buffer board 69 of cushioning effect together is set; change the non-rectilinear path into the linear passages with inlet 606 and liquid outlet 608, fluid changes into along buffer board 69 peripheries and enters liquid stream chamber 632 after impacting this buffer board 69; the fluidic impulsive force that enters liquid stream chamber 632 this moment is just alleviated greatly, effectively group of fibers 620 has been implemented protection.
For the ease of producing, described buffer board 69 is set at inlet 606 and liquid outlet 608 and tube wall 60 intersections, and around the circumferential of tube wall 60 circlewise, further, can also appropriate change tube wall 60 with ring-type buffer board 69 between the space with expansion fluid throughput.
Those skilled in that art can predict, and described airflow chamber 631 can exchange with liquid stream chamber 632, therefore, should regard it as not unconventional spirit and scope of the present utility model.
In the phenolsulfonphthalein test that the applicant carried out, control system of the present utility model demonstrates than prior art and exchanges effect more uniformly, but because of the formed picture of phenolsulfonphthalein test process is a photochrome, do not meet Patent Law about the regulation of accompanying drawing and diagram is not provided, those skilled in that art can test voluntarily to verify that this type of is according to the predictable result of this utility model.
In sum, bioreactor of the present utility model and control system thereof and method, be particularly suited for the bioartificial liver application scenario, problems such as perfusion inequality, dead space, obstruction and exchange rate that the prior biological reactor exists are low have comprehensively been solved, then the multiple control system that is made of different bioreactors is provided, for the biochemical reaction field provides better supplementary instrument.
Above embodiment only in order to the explanation this utility model and and the described technical scheme of unrestricted this utility model; Therefore, although this description has been described in detail this utility model with reference to each above-mentioned embodiment,, those of ordinary skill in the art should be appreciated that still and can make amendment or be equal to replacement this utility model; And all do not break away from the technical scheme and the improvement thereof of spirit and scope of the present utility model, and it all should be encompassed in the middle of the claim scope of the present utility model.
Claims (7)
1. multi-room separated bioreactor, control system comprises:
Bioreactor, it comprises cylindrical shell, mandrel and filter membrane, cylindrical shell forms reative cell and reacts to offer first fluid that has fused first material and second fluid that has fused second material, mandrel traverses drum shaft to setting, the mandrel two ends form second fluidic entry and the exit passageway respectively, this filter membrane coats this mandrel, to stop first material, to allow second material to pass through, forms the slit between filter membrane and the mandrel;
Motor is used to drive described bioreactor around its mandrel rotation;
Storage bottle is used to store second fluid that has fused second material;
Kinetic pump, second fluid that is used for keeping storage bottle enters reative cell after exit passageway is got back to storage bottle to constitute unidirectional closed circuit through the entry of bioreactor;
It is characterized in that:
In this bioreactor, along be coated with filter membrane mandrel be axially arranged with at least two ligation parts reative cell is divided into a plurality of reaction zones, this ligation part is provided with axis hole and passes through for the mandrel that is coated with filter membrane, the radius of ligation part accounts for 3/10 to 7/10 barrier part radius;
Described exit passageway and access road all are connected with each reaction zone separately.
2. multi-room separated bioreactor, control system according to claim 1 is characterized in that:
This mandrel comprises urceolus and inner core, urceolus hollow, and its two ends and cylindrical shell end walls fix, the sealing of one end, the other end is formed with the outer side outlet of described exit passageway, and its surface is axially arranged with some through holes to form the interior side outlet of described exit passageway along it;
Described inner core hollow, its end opposite sealing with the urceolus blind end, the other end and corresponding cylindrical shell end wall fix and form the outer side entrance of described access road, and its surface is axially arranged with some through holes to form the interior side entrance of described access road along it;
The pairing mandrel of each described reaction zone place is equipped with described interior side entrance and interior side outlet.
3. multi-room separated bioreactor, control system according to claim 1 is characterized in that: the radius of described ligation part accounts for 1/2 barrier part radius.
4. multi-room separated bioreactor, control system according to claim 1 is characterized in that: described cylindrical shell is provided with sample tap and application of sample mouth.
5. according to any described multi-room separated bioreactor, control system in the claim 1 to 4, it is characterized in that: this control system also comprises oxygenator, and being used for provides oxygen that the source provides and second fluid of described closed circuit to be combined to oxygen.
6. multi-room separated bioreactor, control system according to claim 5, it is characterized in that: this oxygenator comprises a cylindrical shell, cylindrical shell has a wall and two headwalls reach by they defined synthetic chambeies, synthetic intracavity is provided with the group of fibers of being made up of side by side many doughnuts, the both sides of the longitudinally of this group of fibers and synthetic chamber cementation are to form the liquid stream chamber of passing through for second fluid between cementation position, two places, the hollow cavity of each doughnut forms the airflow chamber that oxygen supply gas passes through jointly, cylindrical shell is provided with air inlet and the gas outlet that is communicated with this airflow chamber, and is provided with inlet and the liquid outlet that is communicated with this liquid stream chamber.
7. multi-room separated bioreactor, control system according to claim 6 is characterized in that, the cross section at described inlet and liquid outlet place is provided with buffer board and enters the liquid stream chamber so that second fluid presents with the non-rectilinear path.
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| CN201020148544XU CN201643112U (en) | 2010-03-19 | 2010-03-19 | Control system of multi-room-divided bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201020148544XU CN201643112U (en) | 2010-03-19 | 2010-03-19 | Control system of multi-room-divided bioreactor |
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| CN201643112U true CN201643112U (en) | 2010-11-24 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101862482A (en) * | 2010-03-19 | 2010-10-20 | 南方医科大学珠江医院 | Multi-room separated bioreactor, control system and method |
| WO2011113220A1 (en) * | 2010-03-19 | 2011-09-22 | 南方医科大学珠江医院 | Bioreactor, control system and method thereof |
| CN113499496A (en) * | 2021-07-14 | 2021-10-15 | 江苏赛腾医疗科技有限公司 | Membrane oxygenator with built-in filter |
-
2010
- 2010-03-19 CN CN201020148544XU patent/CN201643112U/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101862482A (en) * | 2010-03-19 | 2010-10-20 | 南方医科大学珠江医院 | Multi-room separated bioreactor, control system and method |
| WO2011113220A1 (en) * | 2010-03-19 | 2011-09-22 | 南方医科大学珠江医院 | Bioreactor, control system and method thereof |
| CN101862482B (en) * | 2010-03-19 | 2012-10-03 | 南方医科大学珠江医院 | Multi-room separated bioreactor, control system and method |
| CN113499496A (en) * | 2021-07-14 | 2021-10-15 | 江苏赛腾医疗科技有限公司 | Membrane oxygenator with built-in filter |
| US11724014B2 (en) | 2021-07-14 | 2023-08-15 | Jiangsu Stmed Technology Co., Ltd. | Membrane oxygenator with built-in filter |
| JP2023537170A (en) * | 2021-07-14 | 2023-08-31 | 江▲蘇▼▲賽▼▲騰▼医▲療▼科技有限公司 | Membrane oxygenator with built-in filter |
| JP7381773B2 (en) | 2021-07-14 | 2023-11-16 | 江▲蘇▼▲賽▼▲騰▼医▲療▼科技有限公司 | Membrane oxygen supply device with built-in filter |
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